A unique understanding of time-dependent biological processes informs everything we innovate for the treatment of chronic neurologic disorders. We continue to search for time-dependent patterns in diseases to reshape medicines and drive improved clinical outcomes for people in need.

  • We understand and map the complex patterns of disease and drug activity
  • We strive to create medicines which have a therapeutic profile that match the pattern of disease to drive a more significant and durable clinical effect

Our medicines are timed for the benefit of patients.

ADS-5102 (amantadine) extended-release capsules
Multiple Sclerosis: Walking Impairment
Multiple sclerosis (MS) is a chronic autoimmune-mediated disorder that affects approximately 400,000 people in the United States.1 Walking impairment is a central feature of MS progression.2,3,4 The reported prevalence of impaired mobility due to MS ranges from 50% to over 90% of patients.1 As also reported in Parkinson’s disease, dysregulation of the NMDA receptor has been associated with the symptomology of MS,5 therefore symptoms may be improved by modulating overactivated NMDA receptor signaling. As a result, an effective treatment should provide relief beginning in the morning, and be sustained throughout the day, while not disrupting sleep.

ADS-5102, a high-dose amantadine investigational agent taken once-daily at bedtime, was designed to provide a slow initial rate-of-rise in drug concentrations and a delayed time to the maximum concentration.

We completed a Phase 2 proof-of-concept study evaluating ADS-5102 in patients with MS who have walking impairment. In the study, patients treated with ADS-5102 showed a significant improvement in walking speed as assessed by the Timed 25 Foot Walk (T25FW) test and an improvement in the Timed Up and Go (TUG). In addition, ADS-5102 was generally well tolerated.

Based on the positive Phase 2 data, we plan to initiate a pivotal registration program for this indication in the first quarter of 2018.

ADS-4101 (lacosamide)
modified-release capsules
Epilepsy: Partial-onset Seizures
Epilepsy affects an estimated 3.0 million Americans, of which approximately 1.9 million have partial onset seizures.8,9 Monotherapy treatment of partial seizures is effective in approximately 60% of patients, leaving the remainder of patients to require adjunctive treatment with one or more additional anticonvulsant therapies.10,11 There are limited data on the temporal distribution of seizures over the 24-hour day, however, published studies suggest that seizures occur in a diurnal pattern, characterized by a peak between 8 AM and 4 PM, and lowest between midnight and 8 AM.12 Thus, by matching the timing pattern of seizures to the concentration of the anti-epileptic drug, with a higher drug concentration during the day and lower drug concentration during the night, may enable improved seizure control.

Clinical studies of lacosamide, an anti-epilepsy active ingredient previously approved by the U.S. Food and Drug Administration (FDA) and currently marketed by UCB, Inc. as VIMPAT® (lacosamide), have reported dose limitations due to dizziness immediately following administration.13 We hypothesized the dizziness associated with higher doses might be in part attributed to the rapid initial rate-of-rise in drug concentration. Adamas scientists confirmed this time-dependent effect through in vivo modeling and preclinical experiments, showing that tolerability was dependent on rate-of-rise of drug concentration and not on maximum concentrations (Cmax).

ADS-4101, a high-dose lacosamide investigational agent taken once-daily at bedtime, was designed to have a slow initial rate-of-rise in lacosamide concentrations, to potentially improve the adverse event profile. This slow initial rise may enable a higher once-daily bedtime dose, potentially resulting in a higher daytime concentration than VIMPAT.

Data from a Phase 1 study in healthy volunteers showed that a single 400 mg dose of ADS-4101 was better tolerated compared to the equivalent dose of VIMPAT (lacosamide) immediate-release tablets. The data also demonstrated that ADS-4101 exhibited the desired pharmacokinetic properties, namely a reduced rate of initial rise and delayed time to maximum drug concentration (Tmax) appropriate for bedtime dosing.

We conducted a multi-dose Phase 1b study to evaluate the tolerability and pharmacokinetic profile of three ascending doses of ADS-4101 (up to 600 mg/day) taken once-daily at bedtime compared to ascending doses of twice daily VIMPAT tablets in 24 healthy volunteers. Topline data from the Phase 1b study showed that a 600 mg dose of ADS-4101 achieved a 1.7-fold higher lacosamide plasma concentration throughout the day and comparable tolerability relative to the approved maximum daily 400 mg dose of VIMPAT (lacosamide) immediate-release tablets, taken as 200 mg twice-daily, in healthy volunteers. We plan to discuss the next steps for the ADS-4101 program with the FDA at an End-of-Phase 2 meeting.

References: 1. Sutliff, M. H. Contribution of impaired mobility to patient burden in multiple sclerosis. Curr Med Res Opin; 2010 26(1): 109-119. 2. Kurtzke, J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) and Form. Neurology; 1983 33(11):1444-1452. 3. Cohen, R. A., H. R. Kessler, et al. The Extended Disability Status Scale (EDSS) as a predictor of impairments of functional activities of daily living in multiple sclerosis. J Neurol Sci; 1993 115(2):132-135. 4. Hobart, J. C., A. Riazi, et al. Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12). Neurology; 2003 60(1):31-36. 5. Rossi, S., V. Studer, et al. Opposite roles of NMDA receptors in relapsing and primary progressive multiple sclerosis. PLoS One; 2013 8(6):e67357. 6. Cohen, R.A., and M. Fisher. Amantadine Treatment of Fatigue Associated with Multiple Sclerosis. Arch Neurol; 1989; 46:676-680. 7. Socie, M.J., et. al. Gait variability and disability in multiple sclerosis. Gait & Posture; 2013 38:1-55. 8. Hirtz, D., Thurman, DJ., et al. How common are the “common” neurological disorders? Neurology; 2007 68:326-337. 9. Tellez-Zenteno, JF., Ronquillo LH., et al. Discontinuation of antiepileptic drugs after successful epilepsy surgery. Epilepsy Res; 2012 102(1-2):23-33. 10. Kwan, P. B., M. J. Early identification of refractory epilepsy. N Engl J Med; 2000 42(5):314-319. 11. Brodie, M. J., S. J. Barry, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology; 2012 78(20):1548-1554. 12. Hofstra, W. A., B. E. Grootemarsink, et al. Temporal distribution of clinical seizures over the 24-h day: a retrospective observational study in a tertiary epilepsy clinic. Epilepsia; 2009 50(9):2019-2026. 13. Horstmann, R., R. Bonn, et al. Basic Clinical Pharmacologic Investigations of the New Antiepileptic Drug SPM 927. Epilepsia; 2002 43(S7).